| 1. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 4. |
- Kindmark, Andreas, et al.
(author)
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Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis
- 2008
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In: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 8:3, s. 186-195
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Journal article (peer-reviewed)abstract
- One of the major goals of pharmacogenetics is to elucidate mechanisms and identify patients at increased risk of adverse events (AEs). To date, however, there have been only a few successful examples of this type of approach. In this paper, we describe a retrospective case–control pharmacogenetic study of an AE of unknown mechanism, characterized by elevated levels of serum alanine aminotransferase (ALAT) during long-term treatment with the oral direct thrombin inhibitor ximelagatran. The study was based on 74 cases and 130 treated controls and included both a genome-wide tag single nucleotide polymorphism and large-scale candidate gene analysis. A strong genetic association between elevated ALAT and the MHC alleles DRB1*07 and DQA1*02 was discovered and replicated, suggesting a possible immune pathogenesis. Consistent with this hypothesis, immunological studies suggest that ximelagatran may have the ability to act as a contact sensitizer, and hence be able to stimulate an adaptive immune response.
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| 5. |
- Humail, Islam S, et al.
(author)
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Tensile behavior change depending on the varying tungsten content of W--Ni--Fe alloys
- 2007
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In: International journal of refractory metals & hard materials. - : Elsevier BV. - 0263-4368. ; 25:5-6, s. 380-385
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Journal article (peer-reviewed)abstract
- Tungsten heavy alloys (WHAs) are metal–metal composites consisting of nearly pure spherical tungsten particles embedded in a Ni–Fe–W or Ni–Co–W or Ni–Cu–W ductile matrix. In this dual phase alloy, there are several complicated relations between the ductile matrix and hard tungsten particles. The aim of this research was to examine the effect of varying tungsten content on the microstructure and mechanical properties of tungsten heavy alloys. The microstructural parameters (grain size, connectivity, contiguity and solid volume fraction) were measured and were found to have a significant effect on the mechanical properties of tungsten-based heavy alloys. The result shows that the binding strength between the W and the matrix phase has a major influence on the ductility of tungsten-based alloys. The larger this binding force is, the better the ductility is.
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| 6. |
- Kian, L. K., et al.
(author)
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Isolation and characterization of nanocrystalline cellulose from roselle-derived microcrystalline cellulose
- 2018
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In: International Journal of Biological Macromolecules. - : Elsevier B.V.. - 0141-8130 .- 1879-0003. ; 114, s. 54-63
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Journal article (peer-reviewed)abstract
- Roselle fiber is a renewable and sustainable agricultural waste enriched with cellulose polysaccharides. The isolation of Nanocrystalline cellulose (NCC) from roselle-derived microcrystalline cellulose (MCC) is an alternative approach to recover the agricultural roselle plant residue. In the present study, acid hydrolysis with different reaction time was carried out to degrade the roselle-derived MCC to form NCC. The characterizations of isolated NCC were conducted through Fourier Transform Infrared Ray (FTIR), Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FESEM), Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS), Energy Dispersive Spectroscopy (EDS), X-ray Diffraction (XRD), Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). As evaluated from the performed morphological investigations, the needle-like shape NCC nanostructures were observed under TEM and AFM microscopy studies, while irregular rod-like shape of NCC was observed under FESEM analysis. With 60 min hydrolysis time, XRD analysis demonstrated the highest NCC crystallinity degree with 79.5%. In thermal analysis by TGA and DSC, the shorter hydrolysis time tended to produce NCC with higher thermal stability. Thus, the isolated NCC from roselle-derived MCC has high potential to be used in application of pharmaceutical and biomedical fields for nanocomposite fabrication.
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| 7. |
- Kian, Lau, et al.
(author)
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Morphological, physico-chemical, and thermal properties of cellulose nanowhiskers from roselle fibers
- 2019
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In: Cellulose. - : Springer Netherlands. - 0969-0239 .- 1572-882X. ; 26:11, s. 6599-6613
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Journal article (peer-reviewed)abstract
- Abstract: In present study, cellulose nanowhiskers (CNWs) were isolated from roselle fibers by employing low-medium amplitudes of ultrasonication. In a range of low-to-moderate amplitudes of ultrasound, 20%, 30% and 40% amplitudes were applied during ultrasonication treatment to produce CNW-I, CNW-II and CNW-III particles, respectively. The morphological (TEM, FESEM, and AFM), physicochemical (FTIR, EDS, DLS, and XRD) and thermal properties (TGA and DSC) of produced CNWs were conducted to understand the effect of applied amplitudes on CNWs properties. It is clear from the FTIR spectra that increasing ultrasonic amplitudes enhanced crystalline of CNWs. In TEM analysis, CNWs sonicated with 30% and 40% amplitudes possessed the shape of elongated rod-like nanoparticles. FESEM and AFM micrographs exhibited varying whisker-like nanostructures. Additionally, both CNW-II and CNW-III showed stable aqueous colloidal suspensions with zeta potential values more than − 25 mV in response to high sulfur content. As for XRD evaluation, CNW-III exhibited the higher crystallinity degree of 79.9% amongst the all samples. Based on thermal analysis, CNW-I and CNW-II possessed high heat resistant capability at elevated temperature. These CNWs are potential reinforcements in nanocomposites for diverse applications in packaging, engineering, composites and biomedical fields.
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| 8. |
- Musher, Benjamin L., et al.
(author)
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LOAd703, an oncolytic virus-based immunostimulatory gene therapy, combined with chemotherapy for unresectable or metastatic pancreatic cancer (LOKON001) results from arm 1 of a non-randomised, single-centre, phase 1/2 study
- 2024
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In: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 25:4, s. 488-500
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Journal article (peer-reviewed)abstract
- Background Pancreatic ductal adenocarcinoma is characterised by low immunogenicity and an immunosuppressive tumour microenvironment. LOAd703, an oncolytic adenovirus with transgenes encoding TMZ-CD40L and 4-1BBL, lyses cancer cells selectively, activates cytotoxic T cells, and induces tumour regression in preclinical models. The aim of this study was to evaluate the safety and feasibility of combining LOAd703 with chemotherapy for advanced pancreatic ductal adenocarcinoma. Methods LOKON001 was a non-randomised, phase 1/2 study conducted at the Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA, and consisted of two arms conducted sequentially; the results of arm 1 are presented here. In arm 1, patients 18 years or older with previously treated or treatment-naive unresectable or metastatic pancreatic ductal adenocarcinoma were treated with standard 28-day cycles of intravenous nab-paclitaxel 125 mg/m 2 plus gemcitabine 1000 mg/m 2 (up to 12 cycles) and intratumoural injections of LOAd703 every 2 weeks. Patients were assigned using Bayesian optimal interval design to receive 500 mu L of LOAd703 at 5 x 10 10 (dose 1), 1 x 10 11 (dose 2), or 5 x 10 11 (dose 3) viral particles per injection, injected endoscopically or percutaneously into the pancreatic tumour or a metastasis for six injections. The primary endpoints were safety and treatment-emergent immune response in patients who received at least one dose of LOAd703, and antitumour activity was a secondary endpoint. This study was registered with ClinicalTrials.gov, NCT02705196, arm 2 is ongoing and open to new participants. Findings Between Dec 2, 2016, and Oct 17, 2019, 23 patients were assessed for eligibility, leading to 22 patients being enrolled. One patient withdrew consent, resulting in 21 patients (13 [62%] men and eight [38%] women) assigned to a dose group (three to dose 1, four to dose 2, and 14 to dose 3). 21 patients were evaluable for safety. Median follow-up time was 6 months (IQR 4-10), and data cutoff was Jan 5, 2023. The most common treatment-emergent adverse events overall were anaemia (96 [8%] of 1237 events), lymphopenia (86 [7%] events), hyperglycaemia (70 [6%] events), leukopenia (63 [5%] events), hypertension (62 [5%] events), and hypoalbuminaemia (61 [5%] events). The most common adverse events attributed to LOAd703 were fever (14 [67%] of 21 patients), fatigue (eight [38%]), chills (seven [33%]), and elevated liver enzymes (alanine aminotransferase in five [24%], alkaline phosphatase in four [19%], and aspartate aminotransferase in four [19%]), all of which were grade 1-2, except for a transient grade 3 aminotransferase elevation occurring at dose 3. A maximum tolerated dose was not reached, thereby establishing dose 3 as the highest-evaluated safe dose when combined with nab-paclitaxel plus gemcitabine. Proportions of CD8 + effector memory cells and adenovirus-specific T cells increased after LOAd703 injections in 15 (94%) of 16 patients for whom T-cell assays could be performed. Eight (44%, 95% CI 25-66) of 18 patients evaluable for activity had an objective response. Interpretation Combining LOAd703 with nab-paclitaxel plus gemcitabine in patients with advanced pancreatic ductal adenocarcinoma was feasible and safe. To build upon this novel chemoimmunotherapeutic approach, arm 2 of LOKON001, which combines LOAd703, nab-paclitaxel plus gemcitabine, and atezolizumab, is ongoing.
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| 9. |
- Nyberg, F, et al.
(author)
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Interstitial lung disease in gefitinib-treated Japanese patients with non-small-cell lung cancer: genome-wide analysis of genetic data
- 2011
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In: Pharmacogenomics. - : Future Medicine Ltd. - 1744-8042 .- 1462-2416. ; 12:7, s. 965-975
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Journal article (peer-reviewed)abstract
- Aim: To investigate potential relationships between SNPs and acute interstitial lung disease (ILD) events in Japanese non-small-cell lung cancer patients receiving gefitinib. Materials & methods: Japanese non-small-cell lung cancer patients treated with gefitinib from a prospective pharmacoepidemiological cohort with a nested case–control study component (‘CCS’; 52 ILD cases, 139 controls) and a retrospective study (28 ILD cases, 55 controls) were genotyped for nearly 500,000 SNPs. Associations between genotype and ILD were evaluated using Fisher’s exact test and logistic regression modeling, and false discovery rate analysis was used to adjust for the large number of statistical tests. Results: The CCS data provided some false discovery rate evidence that the significance of top-ranking SNPs exceeded levels expected by chance, suggesting some genuine associations. However, replication analyses using retrospective study data were not supportive and there was little evidence of strong genetic associations from a combined analysis. Adjustment of CCS analyses for clinical variables provided little additional convincing evidence. Significant gene–gene interactions between SNP pairs using CCS data were not confirmed in retrospective study replication analyses. Conclusion: Although it is not possible to exclude genetic influences in ILD etiology, common sequence variation is unlikely to explain a major component of ILD risk. Our top results may provide a useful hypothesis-generating starting point for further research. Presented, in part, at the 26th ICPE: International Conference on Pharmacoepidemiology & Therapeutic Risk Management, Brighton, UK, 19–22 August 2010. Original submitted 1 December 2010; Revision submitted 22 February 2011
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